Ptu Induced Failure Of Tooth Eruption In Sd Rats

Ptu 诱导 Sd 大鼠牙齿萌出失败

• 批准号: 6838650
• 负责人: JACK B BISHOP
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6838650
• 关键词: antimetabolites; colony stimulating factor; dental development; dental disorder; developmental genetics; environmental toxicology; immature animal; in situ hybridization; laboratory rat; microarray technology; neuroendocrine system; neurotoxins; thiouracil; thyroid hormones; thyroid inhibitor

A 2-generation reproduction study was completed in 2001 by our NTP RACB contractor, TherImmune, in which the pups from high dose PTU treated rats all died within 4 days following weaning. It was determined that the cause of death was starvation since the incisors of these pups failed to erupt. The pups also exhibited a malformation phenotype similar to that of a knockout mouse known as "toothless". The gene knocked out in this mouse is known as the Colony Stiimulating Factor 1 (aka Macrophage Stimulating Factor 1). This Project proposes to investigate the relationship between the effects of exposure of rats to 0.0015% w/v PTU in drinking water and alterations of CSF-1 and related genes in PND 10-28 day pups. Since PTU induced thyroid hormone disruption is known to be associated with neurological defects, the brains of these rats will also be examined.

我们的NTP RACB承包商Therimmune于2001年完成了两代生殖研究，其中高剂量PTU治疗的大鼠的幼犬在断奶后的4天内都死了。据确定，由于这些幼犬的切牙未能爆发，死亡原因是饥饿。幼崽还表现出类似于被称为“无牙”的敲除小鼠的畸形表型。在这只小鼠中敲出的基因称为集落体育因子1（又称巨噬细胞刺激因子1）。该项目建议研究大鼠在饮用水中暴露于0.0015％w/v PTU的影响与PND 10-28天幼崽中CSF-1和相关基因的改变之间的关系。由于已知PTU诱导的甲状腺激素破坏与神经缺陷有关，因此还将检查这些大鼠的大脑。